Synthesis, Characterization and Biological Evaluation of a Novel Series of 1,2,4-Triazolo-[3,4-b]-1,3,4-thiadiazines Containing an Amide Linkage

Two series of combinatorial library of 3,6-disubstituted-7H-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazines bearing an amide linkage were synthesized. All the newly synthesized compounds were characterized by spectral analyses. The newly synthesized compounds were screened for their cytotoxicity, anti-inflammatory, and analgesic activities. Among the tested compounds, the compound 9g (Ar=4-(methoxybenzyl)piperazine) is the most promising molecule with half maximal inhibitory concentration (IC50) value of 14.24M in (MCF-7) cells. Compounds 9f (Ar=4-(chlorobenzyl)piperazine), 9g, and 9k (Ar=2-(fluorophenyl)piperazine) exhibited excellent anti-inflammatory activity at a dose level of 50mg/kg, almost comparable with the standard drug. In case of analgesic activity among the tested compounds, the compounds 9f, 9g, and 9k showed more potent and consistent activity in both 100 and 200mg/kg/po doses with less ulcerogenic risk.